Vancomycin (VCM) is a glycopeptide antibiotic that is generally used to treat methicillin-resistant Staphylococcus aureus (MRSA). Recently, it has been reported that VCM clearance (CL) is significantly higher in elderly patients and infants and children with malignancies, compared with those without malignancies. We have treated many patients with a variety of malignant tumors in whom serum VCM concentrations were found to be moderately lower during therapeutic drug monitoring (TDM). The aim of this study was to determine whether the presence of malignant tumors influences trough concentrations of VCM and VCM pharmacokinetics in elderly patients during treatment for MRSA infection. Comparison of the clinical characteristics and VCM pharmacokinetic parameters between patients with and without malignancies was undertaken in 49 elderly Japanese patients infected with MRSA. The mean trough concentration of VCM in patients with malignancies was significantly lower than that in patients without malignancies. Our results showed significantly higher values of VCM CL and volume of distribution and a shorter elimination half-life in patients with malignancies. Univariate logistic regression analysis of the pharmacokinetic parameters indicated that VCM CL contributed as a significant factor independent of the relation to malignant tumor. In conclusion, it is suggested that the therapeutic effects and side effects of VCM should be actively monitored using TDM, because concentrations may decrease when CL increases in VCM therapy for elderly patients with malignant tumors.